The overall goals of this research are to improve our understanding of how best to measure glucose metabolism (MRGlc) in malignant gliomas in vivo and to use such measurements for assessing the grade and distribution of malignancy within these tumors at initial presentation, after therapy and at recurrence. Monitoring the results of therapy, chiefly radiotherapy, with glucose metabolic measurements is aimed at defining when clinical benefit or failure has occurred and when radionecrosis has occurred. The readily available tracer, [F-18] fluorodeoxyglucose (FDG), with positron emission tomography (PET) will be evaluated for its utility and accuracy in the clinical management of malignant gliomas. To measure the MRGlc in gliomas with FDG accurately it is necessary to define specifically in the neoplastic tissue the uptake of FDG relative to glucose which includes transport from the plasma and subsequent phosphorylation by hexokinase to FDG-6-phosphate or glucose-6-phosphate respectively. This will be accomplished by dynamic PET studies that successively combine 1-[C-11]-glucose and FDG such that quantitative measurements of MRGlc with 1-[C-11]-glucose can be used to validate the results of FDG studies. Compartmental and distributed mathematical models designed for 1-[C-ll]-glucose and FDG individually will be used for this quantitative analysis. Also, biochemical measurements will be used to validate the PET measurements. For these, surgically removed human gliomas and normal human cortex, removed as part of surgery for intractable epilepsy, will be analyzed for the hexokinase kinetics of glucose and deoxyglucose and calculation of the phosphorylation ratio which defines the relative affinity of hexokinase for the two hexoses. The PET data gathered with 1-[C-11]-glucose will be used to test the hypothesis that there are diagnostic quantifiable patterns of tracer distribution and loss with 1-[C-11]-glucose in gliomas that are distinct from normal brain because of the combined effects of glycolysis to produce lactate and loss of the C1 carbon of glucose via the pentose shunt. The pentose shunt contribution to MRGlc in gliomas will be examined in PET studies that compare the kinetic behavior or 1-[C-11]- vs. 6-[C-11]-glucose. Studies in vitro of human and rat gliomas treated with either 1-[C-14]- or 6-[C-14]-glucose and studies in vivo in subcutaneously transplanted rat gliomas will augment the PET measurements. Lastly, we will test the hypotheses: (a) effective radiotherapy of malignant gliomas reduces the MRGlc sooner than CT or MRI changes indicate a therapeutic response and (b) pre- to immediate post-treatment reduction in MRGlc and immediate post-radiotherapy low tumor MRGlc both predict good therapy outcome. To do this we will image MRGlc before and within two weeks after radiotherapy, and at six months post-radiotherapy, and analyze these images in reference to time to tumor progression and length of survival.